Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.
The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuT(Aa) and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.
Weyand
Simone
S
Membrane Protein Laboratory, Diamond Light Source Limited, Harwell Science and Innovation Campus, Chilton, Didcot, Oxfordshire OX11 0DE, UK.
Shimamura
Tatsuro
T
Yajima
Shunsuke
S
Suzuki
Shun'ichi
S
Mirza
Osman
O
Krusong
Kuakarun
K
Carpenter
Elisabeth P
EP
Rutherford
Nicholas G
NG
Hadden
Jonathan M
JM
O'Reilly
John
J
Ma
Pikyee
P
Saidijam
Massoud
M
Patching
Simon G
SG
Hope
Ryan J
RJ
Norbertczak
Halina T
HT
Roach
Peter C J
PC
Iwata
So
S
Henderson
Peter J F
PJ
Cameron
Alexander D
AD
D000192:Actinomycetales / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006827:Hydantoins / Q000737:chemistry / Q000378:metabolism; D017136:Ion Transport; D008958:Models, Molecular; D008969:Molecular Sequence Data; D033702:Nucleobase Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012964:Sodium / Q000378:metabolism; D027981:Symporters / Q000737:chemistry* / Q000378:metabolism
D001426:Bacterial Proteins; D002412:Cations; D006827:Hydantoins; D033702:Nucleobase Transport Proteins; D027981:Symporters; C031427:5-benzylhydantoin; D012964:Sodium